Hereditary Corpoporphyria Presenting with Deep Jaundice and Photosensitivity
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ANNALS OF GASTROENTEROLOGY 2001, 14(4):319-324 Case report Hereditary corpoporphyria presenting with deep jaundice and photosensitivity D. Kapetanos, P. Xiarhos, E. Kapetis1, A. Avgerinos, A. Ilias, G. Kokozidis, G. Kitis CASE REPORT SUMMARY A 20-year old woman was referred to our department Hereditary coproporphyria is a rare hepatic porphyria with from another hospital in May 2000, due to painless jaun- symptoms similar to acute intermittent porphyria. Photo- dice and pruritus. She reported having dark urine and sensitivity is not described in the latter. We report the case pale stools for two weeks and jaundice for 10 days be- of a young female with deep jaundice, photosensitivity, ane- fore admission. mia, renal failure and no abdominal pain. Hereditary co- proporphyria was diagnosed and the patient was discharged The patient had no past medical history, with no ne- after 111 days in full recovery. She was readmitted after 45 onatal jaundice, had received no medications during the days with abdominal pain and no jaundice or photosensi- previous months and had no alcohol consumption in the tivity. Severe neuropathy developed which caused tetrapare- past. She was on a diet in order to lose weight (her initial sis and deterioration of the respiratory muscle function. weight was 80 kg) and had been using home insecticides Haem arginate was administered with gradual improvement several days before. Her parents reported a family histo- of neuropathy. ry of thalassemia major. Key words: Hereditary corpoporphyria, jaundice, photosen- On admission she was icteric. She had 2-3 blisters on sitivity, neuropathy, haem arginate her face with serous yellow colored fluid. The blood pres- sure was 100/70 mm Hg, the pulse was 60 per minute INTRODUCTION and the temperature was normal. The liver was not pal- pable but the spleen was palpable 2 cm below the costal Hereditary coproporphyria is a very rare hepatic por- margin. There was no lymphadenopathy and no signs of phyria with clinical presentation similar to acute inter- ascites or peripheral edema. Heart sounds and pulmo- mittent porphyria, except that cutaneous photosensitivi- nary auscultation were normal. ty is also present in 30% of cases of the former. We The results of the hematological and biochemical present a young female with acute cholestasis and cuta- analysis on different days of her hospitalization are shown neous photosensitivity without neurological symptoms at in Table 1. HBsAg, anti-HBs, HBeAg, anti-HBe, anti- presentation, who proved to have hereditary copropor- Hbc, anti-HCV, HCV-RNA by PCR, IgM anti-HAV, phyria. anti-HIV1,2, IgM anti-CMV, IgM anti-EBV, IgM anti- HSV1,2 were negative. Antinuclear, antimitochondrial and anti-smooth muscle antibodies were also negative. Gastroenterology Department, George Papanikolaou Hospital, Serum ceruloplasmine was 0,49gr/L (normal 0,22-0,58) Thessaloniki, Greece, 1Histopathology Laboratory, Department of and copper 1,68ìg/ml (normal 0,7-1,4) and 24hour urine Dermatology, Aristotles University of Thessaloniki copper was 300ìg/ml (normal<100). Serum immu- noglobulins were: IgA 126mg/dl, IgG 395mg/dl, IgM Author for correspondence: 69mg/dl. a-1 antithrypsin was 211ìg/dl (93-224). No Keis- George Kitis, 19, Anixeos str., 552 36 Thessaloniki, Greece, Tel.: er-Fleischer rings were detected. Tuberculin test and +31-350102, Fax: +31-350050, e-mail: [email protected] multiple blood cultures were negative. 320 D. KAPETANOS et al Table 1. Hematological and biochemical values Day 1 Day 24 Day 45 Day 66 Day 111 Day 139 Leucocytes k/ìl 7 11,6 10,6 16,7 5 6 Hb g/dl 9,4 6,9 11,8 8,1 8,2 9,8 PLS k/ìl 116 233 91 155 112 120 PT sec 12/12 12,5/10,5 13/10.5 12,8/10,5 10,6/10,5 11/11 LDH IU/L 247 312 401 349 130 143 AST IU/L 57 66 48 85 41 25 ALT IU/L 56 60 80 88 29 17 ã-GT IU/L 13 16 47 29 29 22 ALP IU/L 256 224 190 288 145 148 Protein g/dl 5,8 5,6 6,1 5 6,2 6,9 Albumin g/dl 3,1 3,3 4,3 3,2 4,4 4,6 Bilirubin mg/dl 14,6 47 63,9 45,4 5,8 1,9 Direct bil. 10,35 44 45,8 33,8 4,4 0,58 Glucose mg/dl 92 139 90 85 75 91 Urea mg/dl 17 143 89 76 48 36 K meq/L 4,9 3,4 4 4,1 4,5 4,7 Na meq/L 149 138 136 134 146 145 Creatinin mg/dl 0,9 4,3 1 2,7 0,9 1,1 Blood hemoglobin was 9,4g/dl on admission, but it and compartmentalization of the liver parenchyma. Be- gradually fell to 6,9g/dl. MCV was 63,7, MCH 20,2, cause of these findings she underwent an ERCP, which MCHC 31,6. Reticulocyte count was 2,1%. Serum iron is a much more sensitive diagnostic method than MRCP, was 73ìg/dl and ferritin 18,1ng/ml. Gene analysis by PCR for detecting bile duct abnormalities, that revealed nor- for C282Y and H63D mutations of the hemochromato- mal bile duct appearance. Mild duodenitis was found on sis HFE gene was negative. Direct and indirect Coombs esophago-gastro-duodenoscopy. test were negative. The examination of the G6PD en- The percutaneous liver biopsy showed normal hepatic zyme was normal. Red cell osmotic resistance was in- architecture. There was diffuse cholestasis, mainly ex- creased and the sickle test was negative. Hemoglobin tracellular and marked portal inflammation with poly- electrophoresis was normal. She had no obvious blood morphonuclear cells. The inflammatory cells were de- loss. Twelve units of red cells were transfused during her stroying the wall of the bile ducts and epithelium and hospitalization. A bone marrow aspiration showed in- entered the lumen. There was mild intralobular inflam- creased cellularity, indicating that anemia and thrombo- mation and no fibrosis. cytopenia was caused by peripheral destruction. This was attributed to hypersplenism. Following her admission the jaundice worsened and the blisters extended to the extremities but not the body. Abdominal ultrasound revealed homogenous echo- The fluid in the blisters was yellow at the beginning and genicity of the liver with normal intrahepatic and extra- it subsequently turned to hemorrhagic. The blisters were hepatic ducts. The gallbladder was normal. There was broken to eschars and healed, leaving discoloration of portal and splenic vein dilatation (18mm and 12mm re- the epidermis, while new lesions appeared elsewhere spectively). The spleen diameter was 126mm. (Figure 1, 2, 3). A skin biopsy showed subdermal blisters Computerized tomography of the abdomen and tho- with red cells but no inflammatory cells. The findings rax was performed (without contrast medium, due to in- were compatible to porphyria. tercurrent renal failure). It revealed ground glass appear- A urine porphyrin test was 13943ìg/24h (nor- ance in the right lung with no other abnormal findings. mal<150). Blood, urine and feces samples were sent to MRI of the upper abdomen and MRCP were performed Kings College Hospital (SAS Porphyria Service), Lon- and showed normal bile ducts, with surrounding fibrosis don. The results are shown in Table 2. It was concluded Hereditary corpoporphyria presenting with deep jaundice and photosensitivity 321 that the patient had hereditary coproporphyria. Ten days after her admission she started to develop renal failure with normal urine output. There were no casts or red cells on urine examination. Excretion of so- dium was 39mmol/24h. She underwent plasma exchange and hemodialysis that improved renal function tests but had no effect on jaundice. Fifty days after her admission she developed an un- explained nonproductive cough disturbing her, especially in the supine position, that was not relieved by the usual symptomatic measures. Spirometry was normal. She also developed dystrophic nail changes and alopecia, although she had good nutrition. A liver biopsy performed two months after the first biopsy, showed bile duct proliferation, biliary and fibro- sing piecemeal necrosis and multiple areas with hepato- cellular necrosis. Fibrosis in this biopsy was probably the result of a healing process. The patient showed gradual improvement and was discharged 111 days after her admission, with no jaun- dice or photosensitivity (Figure 4, 5). Forty-five days later she was readmitted to our de- partment with abdominal pain, which, after thorough examination, was attributed to an acute attack of por- phyria. She had no fever, jaundice or photosensitivity. She was given 400gr glucose i.v. daily for a few days with- out improvement. On the contrary, she developed neu- ropathy, which caused tetraparesis and deterioration of the respiratory muscle function although blood gases remained normal. Haem arginate (Normosang) was ad- ministered (3mg/Kg daily for ten days) with gradual im- provement and she was discharged two months after her admission. On February 2001 the patient was last seen in the outpatient clinic and she was able to move her hands and walk with assistance. She had no jaundice or photosensi- tivity. DISCUSSION Hereditary coproporphyria (HCP) is a very rare dis- order. It is inherited in an autosomal dominant mode but fewer than 30% of patients have an acute attack. Its incidence has been estimated in Denmark to be 2 per million,1 in Czech Republic 1:1700002 and in Japan 1:184000.3 The disease usually presents with symptoms identical to those of acute intermittent porphyria (AIP). Figures 1, 2, 3. Skin changes a few days after admission. Photosensitivity resembling that of porphyria cutanea 322 D. KAPETANOS et al Table 2. Porphyrin analysis of urine, blood and faeces samples Random urine 5-aminolaevulinic acid (ALA) 4,8 ìmol/mmol creat (normal <3,8) Porphobilinogen (PBG) 1 ìmol/mmol creat (normal <1,5) Total porphyrin 2770 ìmol/mmol creat (normal <35) Uroporphyrin I 97 nmol/L Uroporphyrin III 52 nmol/L Total uroporphyrin (I+III) 149 nmol/L (normal <24) Heptacarboxylate porphyrin 57 nmol/L (normal <4) Coproporphyrin I 2010 nmol/L Coproporphyrin III 11800 nmol/L Total coproporphyrin (I+III) 13810 nmol/L (normal<115) Urine creatinine 5,6 mmol/L Blood Excitation maximum 401 nm Emission maximum 618 nm Faeces Coproporphyrin I 180 nmol/g dry wt Coproporphyrin III 2750 nmol/g dry wt Total coproporphyrin (I+III) 2930 nmol/g dry wt (normal <46) Dicarboxylate porphyrin (protoporphyrin) 230 nmol/g dry wt (normal <134) tarda (PCT) is seen in about 30 per cent, a finding that viral hepatitis or renal failure.